2012

A Nano Approach to CF Drug Delivery

December 13, 2012

Justin Hanes, Ph.D., a fellow in oncology and neurology at Johns Hopkins prior to joining the faculty in 1998, has focused much of his research on targeted cancer treatments using nanoparticles. Noting that typically less than one percent of chemotherapy cancer treatment goes to a patient’s tumor, with the remainder circulating throughout the body and killing healthy cells, he asks, “Would you poison the entire garden to kill one weed? Unfortunately, that is how most chemotherapy works today.”

In the realm of lung disease, Hanes is also taking a nano approach in targeting the mucosal lining of the lungs. No easy task because mucus, critical in preventing viruses and bacteria from entering tissues, also acts as a sticky barrier to drug-loaded nanoparticles. But Hanes and fellow researchers have created biodegradable nano-sized particles that can easily slip through viscous mucus secretions to deliver a sustained-release medication.

“The major advance here is that we were able to make biodegradable nanoparticles that can rapidly penetrate thick and sticky mucus secretions, and that these particles can transport a wide range of therapeutic molecules,” Hanes said. “Previously, we could not get these kinds of sustained-release treatments through the body’s sticky mucus layers effectively.”

These nanoparticles, adds co-investigator and Johns Hopkins Director of Pediatric Pulmonary Medicine Pam Zeitlin, could be an ideal means of delivering drugs to CF patients.

“Cystic fibrosis mucus is notoriously thick and sticky and represents a huge barrier to aerosolized drug delivery,” says Zeitlin. “But in our study, the nanoparticles were engineered to travel through cystic fibrosis mucus at a much greater velocity than ever before, thereby improving drug delivery.”

Previous research led by Hanes demonstrated that latex particles coated with polyethylene glycol (PEG) could slip past mucus coatings, but latex particles are not practical for drug delivery because the body does not break them down. His group has now developed various types of biodegradable particles composed of an inner core that traps therapeutic agents inside, and a dense PEG outer coating that allows the particles to move easily through mucus. As the particles break down, they release drugs to the targeted tissues, including the lung airways in cases when the particles are inhaled.

Concludes Zeitlin, “This work is critically important to moving forward with the next generation of small molecule- and gene-based therapies.”